{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:08:11Z","timestamp":1791122891325,"version":"4.1.0"},"reference-count":135,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Suzetrigine was approved by the US American Food and Drug Administration in 2025 as the first oral, non-opioid, selective inhibitor of NaV1.8 sodium channel for the treatment of acute pain. Therefore, it represents a groundbreaking advancement in pain management. This review aims to provide an overview of the milestones in the medicinal-chemical development of NaV1.8 inhibitors, eventually leading to suzetrigine. The multi-step synthesis route of suzetrigine is presented. Taking structural features into account, insights are provided into what plays a role for the inhibition of the NaV1.8 channel. In addition, pharmacodynamic and pharmacokinetic aspects of the new drug, such as bioavailability, metabolism, and interaction with CYP450 enzymes, are discussed. A summary based on a large number of clinical trials demonstrating remarkable efficacy completes this comprehensive drug profile of suzetrigine, while also addressing limitations of the clinical trials and suggesting future perspectives.<\/jats:p>","DOI":"10.3390\/molecules31020358","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:36:33Z","timestamp":1768898193000},"page":"358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Suzetrigine, a NaV1.8 Inhibitor as a Novel Approach for Pain Therapy\u2014A Medicinal and Chemical Drug Profile"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0818-7469","authenticated-orcid":false,"given":"Rawan M.","family":"Medhat","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria 21648, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8981-4973","authenticated-orcid":false,"given":"Omnia A.","family":"Kotb","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria 21648, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1963-9838","authenticated-orcid":false,"given":"Daniel","family":"Baecker","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universit\u00e4t Berlin, K\u00f6nigin-Luise-Stra\u00dfe 2+4, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1056\/NEJMoa2209870","article-title":"Selective Inhibition of NaV1.8 with VX-548 for Acute Pain","volume":"389","author":"Jones","year":"2023","journal-title":"N. 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